Are scientists finally about to beat dementia?



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In the depths of the Andes, in a coastal city called Yarumal, 5,000 people are at risk of developing Alzheimer's at age 40. Locals say they are cursed with La Bobera, or "silly," a spell that makes people lose their heads.

But they do have a genetic mutation that causes early-onset Alzheimer's.

This high probability of developing the disease means that scientists can justify testing experimental drugs in the hope that this will lead to new drugs.

Dementia affects 850,000 people in the United Kingdom, and this number will increase to 1 million in the next decade. About half a million suffer from the most common form, Alzheimer's disease, without a cure.

  Urgent problem on the rise: dementia affects 850,000 people in the United Kingdom, and this number will increase to 1 million in the next decade

  Urgent problem on the rise: dementia affects 850,000 people in the United Kingdom, and this number will increase to 1 million in the next decade

Urgent problem on the rise: dementia affects 850,000 people in the United Kingdom, and this number will rise to 1 million in the next decade

Part of the difficulty in finding One cure is that we do not detect it early enough, says Gordon Wilbad, professor emeritus of geratology at the University of Oxford. By the time the symptoms begin, the brain has already suffered a lot of damage, so the drugs have little effect, he adds.

The other problem is that we still do not understand what causes Alzheimer's. Although amyloid plaques (sticky buildups in the brain) seem to play a role, it is clear that there are many other factors.

"It may not even be a disease," says Professor Wilbad. He says that the brain of Alzheimer's can be an end point to which people turn in different ways, which means that there may never be a single medicine.

Despite many promising animal studies, no drug has managed to stop the disease in humans Earlier this year, the pharmaceutical giant Merck suspended a test of one of the most promising drugs, verubecestat, after which an external plate determined that there was virtually no chance of it working.

This occurred a few months after another drug that bursts amyloid, solanezumab, was abandoned after poor results.

After 20 years of failed drug trials, you would be forgiven for thinking that it is a lost cause. However, the tide has begun to change with a series of findings that offer new insights and reveal some tantalizing new treatment possibilities.

  A disease without a cure: around half a million suffer from the most common form, Alzheimer

  A disease without a cure: around half a million suffer from the most common form, Alzheimer

A disease without cure: about half million suffer from the most common form, Alzheimer

Researchers at the University of Antioquia in Colombia are testing whether a drug called crenezumab can delay, or even stop, the condition in about 300 Yarumal villagers without symptoms carrying the mutation. The drug contains an antibody, a protein that binds to a specific target, which destroys amyloid.

This is one of the key studies that enters a new field of research to prevent the disease, not just treat its symptoms.

I think we're on the threshold of a breakthrough, "says Lary Walker, badociate professor of neurology at Emory University School of Medicine in the US

. There's a whole research portfolio that reveals more about Alzheimer's disease, why cold can accelerate the disease to how young blood injections can help, here we summarize some of the new findings that can finally solve the enigma of Alzheimer's.

A SOLUTION PROMETHEDER …

The conventional view is that Alzheimer's disease is characterized by proteins called amyloid beta and tau that fold incorrectly and accumulate in adhesive plaques in the brain.

These proteins exist in a natural: beta amyloid has a role in the antimicrobial activity and transport of cholesterol in the brain, but it is when its role is disrupted that it causes problems.

they strangle brain cells called neurons, preventing them from transmitting messages. They also trigger the destruction of healthy brain tissue. Scientists are discovering that this may start years before symptoms like memory loss are noticed. Understanding how this process begins can be key to preventing Alzheimer's.

"One of the challenges is that we still do not know what normal physiological aging is like and how it compares to Alzheimer's," says Delphine Boche, professor of neuroimmunopathology. at the University of Southampton. "We have to understand normal changes much better to solve what is abnormal."

  Frustrating: Recently, Merck stopped a test of one of the most promising drugs, verubecestat, after an external plate determined that there was virtually no chance of it working

  Frustrating: Recently, Merck stopped a test of one of the most promising drugs, verubecestat, after an external plate determined that there was virtually no chance of it working

Frustrating: Recently, Merck stopped a test of one of the most promising drugs, verubecestat, after an external plate determined that there was practically no possibility of it working

The solution seems simple: eliminate these toxic proteins and fix the disease. However, it is much more complex. No drug has managed to eliminate any of the proteins effectively and stop the disease in humans.

In many cases, despite rinsing plates in animals, the drugs fail in human trials due to side effects such as brain inflammation; or do not lead to better brain function.

But a drug, for now, seems to be exceeding the trend.

In a small study conducted by the developers, Biogen, which involved 166 people, aducanumab, an antibody that like crenezumab binds to misfolded amyloid and sends signals to immune cells to get rid of it from the brain, it seems that removes plaque and slows down cognitive decline. It is the first to have a statistically significant effect on both the cognition and the volume of the plate. The results have been considered "unusually robust" by Alzheimer & # 39; s Research UK. But more trials are needed to determine its long-term effectiveness, says Professor Wilbad.

& # 39; It's too early to say if it's as promising as the manufacturer would lead us to believe. & # 39; Larger trials have begun and if successful, may be available within ten years.

LOOKING AT WRONG PLACES

Some scientists believe that plaques and tangles are not the whole story. For example, studies that have examined the brain of Alzheimer's disease have shown that there are groups of immune cells called microglia entangled between the amyloid plaques.

Microglia kills external invaders and toxic waste. But by doing so, they activate inflammatory pathways, which help repair damaged tissue. If left unchecked, excessive inflammation can cause the cells to vomit a toxic substance that kills the surrounding cells.

Microglia happily destroys the amyloid plaques that accompany the early stages of the disease.

  Progress? Researchers at the University of Antioquia in Colombia are testing whether a drug called crenezumab can delay, or even stop, Alzheimer's

  Progress? Researchers at the University of Antioquia in Colombia are testing whether a drug called crenezumab can delay, or even stop, Alzheimer's

Progress? Researchers at the University of Antioquia in Colombia are testing whether a drug called crenezumab can delay, or even stop, Alzheimer's

The theory is that, in some people, the microglia becomes too sensitive and reacts to inflammation or infection in other people. body parts, even the common cold. This can trigger a vicious circle of inflammation and more degeneration of healthy brain cells.

Why microglia turn impish is not clear. But this explains why people who have disorders badociated with inflammation, such as diabetes, cardiovascular problems and autoimmune disorders, have a higher risk of Alzheimer's.

It has been shown that when people with Alzheimer's have some type of infection, they decrease more quickly and when the infection clears their health it does not return to the way it was before, "says Professor Boche. in microglia and in the function of inflammation in the rest of the body.

GROWTH OF NEW CEREBRAL PARTS

Researchers at the University of Aston in Birmingham believe that it is possible Grow segments of brain tissue human that could one day be used to repair the damage caused by Alzheimer's.

These "micro-brains" are made from human skin cells that have become stem cells, which can become almost any cell in the body, and then in neurons using a badtail of chemicals.

The new cells are then grown on scaffolds printed in 3D in groups that resemble the structure of the brain. Currently, the goal is to grow brain tissue to use as a model to try new treatments and learn more about dementia. Someday the technique could even be used to produce brain tissue to replace the one he lost due to illness.

ULTRASOUND COULD HELP

In Canada, a team has been using ultrasound to open the blood brain barrier, a protective envelope that surrounds the brain.

It is formed by a tight layer of cells, which prevents viruses, bacteria and other toxins from pbading into the brain, while allowing the entry of vital molecules, such as nutrients. [19659002] Obtaining drugs through this barrier and in the brain is difficult, so it would be useful to temporarily open it. To break the barrier, the researchers first injected tiny bubbles filled with gas into the blood. Then they directed low level ultrasound waves on the skull with the effect of vibrating the bubbles.

  Expensive care: the UK spends more than £ 30 million per day on the treatment and care of patients with dementia

  Expensive care: the UK spends more than £ 30 million per day on the treatment and care of patients with dementia

Expensive care: the UK spends more than £ 30 million a day on the treatment and care of patients with dementia

This shakes the cells of the blood-brain barrier are separated, allowing the temporary entry of larger molecules, as possible pharmacological treatments.

For now, the Sunnybrook Health Sciences Center team in Toronto is testing the safety of the procedure in six patients, without injecting active drugs.

& # 39; This could lead to revolutionary ways of treating the disease & # 39; says Sandra Black, a scientist who runs the trial.

Merely interrupting the barrier can benefit people with Alzheimer's, as it seems to stimulate nearby immune cells to destroy amyloid, he says.

If it works, patients may receive ultrasound sessions and no drug treatment.

THE YOUNG BLOOD STOPS THE DAMAGE [19659002] OVER in the USA. UU Scientists are testing whether young blood injections can reverse Alzheimer's.

The emerging company Ambrosia administered 70 people with more than 35 blood plasma transfusions taken from people between 16 and 25 years old.

Blood tests taken before and after treatment showed that the markers of several diseases had declined, according to a presentation at the Recode conference in Los Angeles earlier this year.

There was a 20% decrease in amyloid protein levels, a small drop in cholesterol and in proteins badociated with cancer.

Participants also reported benefits in cognition, muscle strength and energy levels. However, the study was criticized for not comparing the results with a placebo treatment.

This month, the results of another trial at Stanford University, in which patients received blood plasma from people 18 to 25 years old, revealed improvements in mental abilities. However, this trial was also criticized for the lack of a placebo.

& # 39; We need to see much larger studies before we can say if this interesting approach could help improve the lives of people living with Alzheimer's disease & # 39; says Dr. Carol Routledge, director of Research in Alzheimer & # 39; s Research UK. It is not clear which component of the blood might be driving these changes, but if it can be isolated, it might be possible to create a drug from them.

ANCIENT DRUGS, NEW TRICKS

& # 39; Your risk of Alzheimer's is lower than it used to be, "says Professor Wilbad," because we now have better tests and treatments for the diseases that predispose us to Alzheimer's, such as diabetes and high blood pressure. "[#19659002] # 39; Perhaps the medications we're taking for these other conditions have an impact on the inflammation badociated with Alzheimer's, "he adds.

And there's more good news, he says: we may already have some of the tools that we need to fight the disease. "The most interesting avenue of research at this time is the idea of ​​reusing existing drugs."

For example, it has been shown that antibiotic minocycline, used to treat acne, and antidepressant medication trazodone improves the symptoms of Alzheimer's disease in mice.

An article published in the journal Brain found that mice that received trazodone showed improvements in the memory and a reduction in brain tissue degeneration. Minocycline seems to suppress the action of microglia, while trazodone seems to affect the production of proteins in the brain.

& # 39; These drugs have been used in humans for years and we know they are safe, so if studies show that they can reduce the symptoms of Alzheimer's disease, you should be able to take them to patients in three to five years, "says Professor Wilbad.

" We have to wait for the results of clinical trials, but until then, there is much we can do to reduce the risk of Alzheimer's, "he says. "If people start to take their lifestyle seriously, exercise more, reduce their weight and get cholesterol and diabetes tests, they will reduce the risk."

"In this way, if the plates and knots appear, you will have a healthier brain that can resist any change for a longer time."

DEMENTIA'S OUR MOST MURDERER. HOME OF FUNDS?

The United Kingdom spends more than £ 30 million per day on the treatment and care of patients with dementia.

This huge amount of money is what is needed to cover everything from medications that alleviate symptoms to the personal care that the country needs 850,000 patients with dementia.

To put this in perspective, the daily bill for other major diseases is around £ 14 million for cancer, £ 8 million for stroke and £ 6.8 million for heart disease Dementia costs more than the three combined.

It would be reasonable, therefore, to expect a similar break in the way the research is funded.

But according to a study at the University of Oxford, dementia receives a fraction of the amount allocated to cancer research and less than that awarded to heart disease, although, in 2016, dementia became the leading cause of death in the United Kingdom, and He claimed more than 70,000 lives.

Investigators observed how an annual amount of £ 856 million funds were divided, cash provided by the government and charities. Almost two thirds (£ 544 million) were given to scientists working on possible cancer treatments and about 20% (£ 166 million) went to research on heart disease.

Dementia received only 11% of the pot (£ 90 million).

Scientific experience follows money, so since dementia has lacked money for research, it has also been denied the skilled labor it requires.

For every four scientists in the UK who work on possible cures for cancer, there is only one doing the same thing in dementia.

This lack of resources, some say, partly explains why the search for new treatments is fraught with failures.

A succession of promising new therapies designed to address brain deposits called amyloid plaques, which are thought to be a major factor in Alzheimer's disease, failed.

"This is what happens when you do not have enough investment," says Dr. David Reynolds, scientific director of Alzheimer & # 39; s Research UK. [19659002] & # 39; You have to decide which is the best option available to spend your limited resources.

& # 39; In dementia, these were amyloid-reducing drugs. But no effective drugs have been produced from all that research. "

So, why is insanity so neglected? In part, according to experts, it's the misperception that it's an inevitable part of aging, what is not profitable.

Aging is the main risk factor for the disease, but there is nothing inevitable about it, says Dr. Reynolds. "Dementia is at the stage when heart disease was in the Seventies, or cancer in the nineties, "he explains.

" It was then that they saw huge investments in research funds that led to revolutionary drugs many years later. "19659002] Things are getting better. David Cameron challenged scientists to find a cure by 2025. Since then, government funding for research has doubled to more than £ 60 million per year.

Other £ 250 m Illones: from charities and the Medical Research Council – has been invested in a new UK Dementia Research Institute, based at University College London.

But some fear that science is trying to find a cure for a disease it does not yet understand.

Dr James Pickett, head of research for the Alzheimer's Society, says: "Most of the money went to molecules that reduce amyloid because they were judged to be the best candidates."

& # 39; But we may not have devoted enough time or money to understand the progression of the disease.

Now we know that when it starts to show symptoms, dementia has been developing for 20 years. a medication. "

Dr. Pickett says that about one in three cases of dementia is potentially preventable, primarily through lifestyle modifications such as a healthy diet.

& # 39; However, the amount of research on prevention of dementia is unfortunate, it is a parody. "

There are about 80 drugs for dementia in phase two or three trials (which are tested in patients)." But the portfolio of new cancer treatments has more than 1,000 new drugs, "says Dr. Reynolds .

Even if a new treatment is discovered, Hilda Hayo, executive director of the charity Dementia UK, warns: "There are 200 different types of dementia." A "magic pill" will not help everyone. , 850,000 people living with the disease need more help and support now. "

By PAT HAGAN

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